Preparation method of lenalidomide

Abstract

The invention relates to the field of drug synthesis, and particularly relates to a preparation method of a lenalidomide intermediate and lenalidomide. The compound is a drug for treating multiple myeloma. The method comprises the steps of adopting 2-bromomethyl-3-nitrobenzoate and 3-amino-2,6-piperidione hydrochloride as reaction substrates and an inorganic base as an acid-binding agent and obtaining a white to almost white key intermediate 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindole-2-yl) piperidine-2,6-diketone of the lenalidomide through simple post-treatment; and adopting a mixed solvent of an organic solvent and water as a reaction solvent and carrying out catalytic hydrogenation in the presence of palladium on carbon to prepare the lenalidomide (II). The process route is low in production cost, and a product is high in purity and friendly to environment, and has relatively great implement value and social and economical benefits.

Description

technical field

[0001] The invention relates to the field of drug synthesis. It specifically relates to the key intermediate 3-(4-nitro-1-oxoisoindol-2-yl)piperidine-2,6-dione and its compound for the treatment of multiple myeloma drug lenalidomide A novel preparation method of lenalidomide. Background technique

[0002] The chemical name of lenalidomide is 3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione ( II) was developed by the US Cell Gene Company and was approved by the US FDA for marketing in January 2006. The drug is used to treat myelodysplastic syndrome (MDS) subtypes with 5q deletion (a gap gene deletion on the long arm of chromosome 5) and multiple myeloma. The structural formula of lenalidomide is as follows:

[0003]

[0004] 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione (I) is a synthetic lenalidomide (II ) important intermediate, the structural formula is as follows:

[0005]

[0006] Fang Feng, Xu Xu, Ji Yaf...

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